Resting and exercise-induced IL-6 levels in children with Type 1 diabetes reflect hyperglycemic profiles during the previous 3 days

Abstract

Poor glycemic control in Type 1 diabetes (T1DM) causes long-term cardiovascular complications, at least in part via chronic, low-grade inflammation associated with recurrent hyperglycemia. While physical activity can reduce both inflammation and cardiovascular risks, the underlying molecular mechanisms remain unclear. This is particularly important for T1DM children, for whom the prevention of long-term cardiovascular complications must include optimization of exercise-related anti-inflammatory strategies. We therefore studied the effect of prior hyperglycemia on resting and exercise-induced inflammatory status (plasma IL-6) in T1DM children. Glycemia was continuously recorded with a continuous glucose monitoring system (CGMS) system for 63 h preceding a 30-min intermittent cycling exercise protocol at approximately 80% peak rate of oxygen uptake (VO2max). Euglycemia (4.4-6.1 mM) was maintained for 90 min before, during, and 30 min after exercise. IL-6 plasma concentration (pg/ml) was measured at baseline, at end exercise, and 30 min postexercise. Subjects were then divided into quartiles based on average glycemia during the CGMS recording. IL-6 levels (pg/ml) were lowest in the quartile with lowest average 3-day glycemia and increased proportionally to greater hyperglycemic exposure; this was observed at baseline (0.86 +/- 0.10, 1.06 +/- 0.16, 1.14 +/- 0.14, 1.20 +/- 0.16), absolute IL-6 change (Delta) at end exercise (0.20 +/- 0.16, 0.32 +/- 0.10, 0.48 +/- 0.09, 0.62 +/- 0.13), and Delta at 30 min postexercise (0.49 +/- 0.13, 0.71 +/- 0.16, 0.89 +/- 0.14, 1.38 +/- 0.33). Therefore, poorly controlled glycemic profile, even in the 63 h preceding an exercise challenge, can alter inflammatory adaptation in T1DM children. Our data underscore the necessity to fully understand all molecular aspects of physical activity to provide the scientific rationale for exercise regimens that will be able to maximize health benefits for T1DM children.

Fig. 1.

Schematic of the experimental design; plasma glucose was continuously monitored for the 3 days preceding study procedures. On study day, glucose stabilization (4.4–6.1 mM) was achieved and maintained for 90 min before, during, and 30 min postexercise [10 bouts of 2-min cycling at ∼80% peak oxygen uptake (V̇o_2max), followed by 1 min rest]. IL-6 was measured at baseline, end exercise, and 30 min postexercise.

Fig. 2.

Representative continuous glucose monitoring system (CGMS) tracings from 2 study subjects: 1 with good glycemic control (top; 3-day average 6.0 mM, no glucose reading above >11.1 mM) and 1 with poor glycemic control (bottom; 3-day average 13.8 mM; 40 h spent >11.1 mM, 31 h >13.9 mM, 19 h >16.7 mM).

Fig. 3.

Mean IL-6 concentrations, at rest and after exercise, from 47 studies in children with Type 1 diabetes, subdivided in quartiles I–IV based on mean prior 3-day glycemia [absolute values (left) and exercise-induced increases (right)]. Open bar, quartile I; light gray bar, quartile II; dark gray bar, quartile III; black bar, quartile IV. Data are group means ± SE. *P < 0.05 vs. quartile I.

Fig. 4.

Mean IL-6 concentrations, at rest and after exercise, from 47 studies in children with Type 1 diabetes, subdivided in quartiles based on hours spent with glycemia >11.1 mM (A); hours spent with glycemia >13.9 mM (B); hours spent with glycemia >16.7 mM (C); and same-morning peak glycemia (D). Data are group means ± SE. Open circles, quartile I; light gray circles, quartile II, dark gray circles, quartile III; black circles, quartile IV. *P < 0.05 vs. quartile I. †P < 0.05 vs. quartiles I and II.

Fig. 5.

Plot of average 3-day glycemia vs. hours spent with glycemia >11.1 in 47 studies in children with Type 1 diabetes.

Fig. 6.

Mean IL-6 concentrations, at rest and after exercise, from 29 studies in children with Type 1 diabetes who had morning hyperglycemia (>11.1 mM) on study day. Children were then subdivided into 2 groups according to their mean glycemia over the previous 3 days. A: ●, morning HyG and 3-day glycemia quartiles III–IV; ○, morning HyG and 3-day glycemia quartiles I–II. B: filled bar, morning HyG and 3-day glycemia quartiles III–IV; open bar, morning HyG and 3-day glycemia quartiles I–II. Data are group means ± SE. HyG, hyperglycemia. *P < 0.05 vs. group with lower prior 3-day mean glycemia.